Hydroximic Acid Derivatives: Pleiotropic Hsp Co-Inducers Restoring Homeostasis and Robustness
| Autor: | Gábor Nagy, Burcin Gungor, Laszlo Koranyi, Bianca J. J. M. Brundel, Zsolt Török, Noémi Tóth, Linda Greensmith, Attila Glatz, Kálmán Tory, Ibolya Horváth, Jean Paul Seerden, Stefano Piotto, Simona Concilio, Imre Gombos, Ákos Hunya, Zsuzsanna Literati-Nagy, Tim Crul, Mária Péter, Harm H. Kampinga, Zoltán Szilvássy, Zoltán Berente, Balazs Sumegi, Gábor Balogh, Philip L. Hooper, József Mandl, Irma Kuipers, Federica Campana, Robert H. Henning, Roelien A. M. Meijering, László Vígh, Femke Hoogstra-Berends, Lizette Loen, Pierre Haldimann, Peter Literati-Nagy, Bernadett Kalmar, Mark A. Febbraio, Deli Zhang, André Heeres, Ferenc Gallyas |
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| Přispěvatelé: | Biobased Ingredients and Materials, Groningen University Institute for Drug Exploration (GUIDE), Molecular Neuroscience and Ageing Research (MOLAR), Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT) |
| Rok vydání: | 2012 |
| Předmět: |
Membrane lipids
NF-KAPPA-B ACETAMINOPHEN-INDUCED HEPATOTOXICITY Drug development Pharmacology HEAT-SHOCK-PROTEIN BGP-15 Neuroprotection POLY(ADP-RIBOSE) POLYMERASE-1 PARP-1 OBSTRUCTIVE PULMONARY-DISEASE AMYOTROPHIC-LATERAL-SCLEROSIS Hydroximic acid derivatives Membrane Lipids Heat shock protein POSTOPERATIVE ATRIAL-FIBRILLATION APOPTOSIS-INDUCING FACTOR Oximes Drug Discovery Medicine Animals Homeostasis Humans Geranylgeranylacetone derivatives Heat shock Lipid raft Heat-Shock Proteins business.industry biochemie Stress response Lipid microdomain Genetic Pleiotropy Atrial fibrillation TRANSGENIC CAENORHABDITIS-ELEGANS Insulin sensitizer BETA-AMYLOID PEPTIDE business Heat-Shock Response |
| Zdroj: | Current Pharmaceutical Design, 19(3), 309-346 Current Pharmaceutical Design, 19(3), 309-346. Bentham Science Publishers Current Pharmaceutical Design, 19(3), 309-346. BENTHAM SCIENCE PUBL LTD Current Pharmaceutical Design 19 (2013) 3 Scopus-Elsevier |
| ISSN: | 1381-6128 |
| DOI: | 10.2174/1381612811306030309 |
| Popis: | According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy. |
| Databáze: | OpenAIRE |
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